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Eur J Immunol. 1995 Dec;25(12):3437-44.

Definition of sites on HLA-DR1 involved in the T cell response to staphylococcal enterotoxins E and C2.

Author information

1
Department of Immunology, Royal Postgraduate Medical School, Hammersmith Hospital, London, GB.

Abstract

We have exploited the relative inefficiency of interaction between staphylococcal enterotoxins, SEE or SEC2, and H-2Ek compared to HLA-DR1 molecules to deduce which regions of the major histocompatibility complex (MHC) class II molecule are involved in the T cell response to these superantigens. Transfectants expressing hybrid DR/H-2E MHC class II molecules were used to present SEE to the T cell receptor V beta 8.1-expressing Jurkat cell line, and SEC2 to human peripheral blood T cells. For SEE, the critical region of the class II molecule for T cell reactivity and for binding was the beta 1 domain alpha-helix. The functional data were corroborated by measurements of direct binding. Sequence comparison between DR and H-2E raised the possibility that the glutamic acid at position 84 in the beta chain of H-2Ek, in place of glycine was responsible for the observed functional effects. This suggestion was supported by the finding that DQw2 (glutamine at 84) transfectants supported the SEE response much more efficiently than DQw6 that has glutamic acid at this position. In addition, amino acid substitutions at either position 36 or 39 in the DR alpha 1 domain abolished T cell reactivity without any obvious alteration in binding. For SEC2, use of transfectants expressing exon-shuffled alpha and beta chain genes showed that replacement of the alpha 1, alpha 2 and beta 1 domains with H-2E sequence inhibited the presentation of SEC2. Similarly, the substitutions at positions 36 and 39 in the alpha 1 domain abolished the T cell response to SEC2. Taken together, these data may be best explained by a model in which these two toxins have primary binding sites on the beta 1 domain (SEE) and the alpha 1 and alpha 2 domains (SEC2), but by virtue of a secondary binding site on the opposite surface of the class II molecule, cross-link two adjacent DR molecules. Such cross-linking may be important in the induction of T cell reactivity.

PMID:
8566035
DOI:
10.1002/eji.1830251235
[Indexed for MEDLINE]

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